BY M E L I S S A JA KU BO W S K I

PULMONARY DISEASE TREATMENT CONCERNING

COPD

AGENDA

Introduce the journal article Review of preliminary backgroundDiscuss the details of the studyEvaluation of the studyDiscuss how the implications of the study translate into practice

Questions

JOURNAL ARTICLE

• Efficacy of corticosteroid therapy in patients with an acute exacerbation of chronic obstructive pulmonary disease receiving ventilatory support

THIS STUDY ASSESSED:

•The effect ofsystemic corticosteroids on ICU patients who were mechanically ventilated (invasive or noninvasive) due to COPD exacerbations

IMPORTANCE

• Previous randomized trials assessing the effect of systemic corticosteroid therapy on COPD exacerbations have excluded patients with respiratory failure who required mechanical ventilation or ICU admission• Critically ill patients in the ICU are more

prone to develop complications potentially associated with corticosteroid therapy

HOSPITAL TREATMENT FOR COPD

•Bronchodilators•Antibiotics•Oxygen•Corticosteroids

COPD AND CORTICOSTEROID THERAPY

• COPD: airways damaged interfering with the exchange of oxygen and carbon dioxide in the lungs

• Function: reduce lung and bronchial tube inflammation related to tissue damage and improve respiratory function

SHORT-TERM SIDE EFFECTS

• Increased appetite• Fluid retention•Weight gain• Increased blood pressure•Hyperglycemia

SYSTEMIC STEROIDS, CORTICOSTEROIDS

• Prednisone• Prednisolone• Methylprednisolone• Betamethasone • Beclamethasone• Dexamethasone• Flurocortisone• Hydrocortisone• Triamcinolone

SCREENING FOR SUBJECTS

• Screening: 354 patients from 8 hospitals in 4 countries from July 2005 – July 2009• Criteria: hospitalization because of

exacerbation of COPD requiring ventilatory support in the ICU• Controls: diagnosis of “exacerbation of

COPD” was explicitly defined; patients with conditions that would alter integrity of study were excluded

ETHICS•Approved by the ethics committee at each hospital•Written informed consent obtained from patients or their surrogates

STUDY POPULATION

354 patients screened for

eligibility

46 Patients with conventional mechanical ventilation

37 Patients with noninvasive mechanical ventilation

271 (76%) patients excluded

165 Steroid treatment42 Pneumonia

23 Refused consent34 Other

BASELINE CHARACTERISTICSCharacteristic Placebo Group

(n=40)Corticosteroid Group (n=43)

P Value

Age (year) 67.6 69.1 0.52

Men (%) 34 32 0.23

SAPS II 36.3 36.3 0.99

Comorbid condition (%)• DM 22 35

0.07

Reason for acute exacerbation of COPD (%)

0.72

Initial ventilatory support (%)

0.60

Blood gases 0.72

Blood glucose (mg/dL)

158.7 193.3 0.02

STUDY DESIGN• Within 24 hours after ICU admission,

patients randomly assigned to either corticosteroid group or placebo group

46 Patients with conventional mechanical

ventilation

25 Patients assigned to

receive corticosteroids

21 Patients assigned to

receive placebo

19 Patients assigned to

receive placebo

18 Patients assigned to

receive corticosteroids

37 Patients with noninvasive mechanical

ventilation

LENGTH OF ADMINISTRATION: 10 DAYS

Treatment Group

• Methylprednisolone

Placebo Group

• Normal saline solution

ADMINISTRATION REGIMEN

Days 1-3

• 0.5 mg/kg every 6 hours

Day 4-6

• 0.5 mg/kg every 12 hours

Days 7-10

• 0.5 mg/kg per day

OUTCOME MEASURES

• Duration of mechanical ventilation, d• Length of ICU stay, d• Length of hospital stay, d• In-ICU mortality, %• Failure of NIMV, % • Reintubation within 48 hours of planned extubation and received CMV either initially or after failure of NIMV, %

FREQUENCY OF ADVERSE EVENTS

•Superinfection•Gastrointestinal bleeding•Arterial hypertension•Hyperglycemia•Ventilator-associated pneumonia•Delirium• ICU-acquired paresis

OTHER DAILY MEASUREMENTS

•ABG analysis•C-reactive protein•Maximal blood glucose level•Daily dose of insulin•PEEP (positive end-expiratory pressure): only in patients who were intubated

RESULTS: OUTCOME MEASURESOutcome Placebo Group Corticosteroid

GroupP Value

Duration of mechanical ventilation, d

4 3 0.04

Length of ICU stay, d

7 6 0.09

Length of hospital stay, d

15 13 0.30

In-ICU mortality, %

10 12 0.81

Failure of NIMV, %

37 0 0.004

Reintubation within 48h, %

19 14 0.71

REDUCTION IN DURATION OF MECHANICAL VENTILATION

Corticosteroid Group Placebo Group0

1

2

3

4

5

Da

ys

REDUCTION IN THE INCIDENCE OF NIV FAILURE

Corticosteroid Group Placebo Group0

5

10

15

20

25

30

35

40

NIV

Fa

ilu

re,

%

FREQUENCY OF ADVERSE EVENTS

Event Placebo Group Corticosteroid Group

P Value

Superinfection 6 5 0.65

GI bleeding 2 2 0.60

Arterial HTN 4 2 0.42

Hyperglycemia 10 20 0.04

Vent-associated pneumonia

3 4 0.77

Delirium 3 1 0.35

ICU-acquired paresis

0 0 …

PROS VS. CONS

Pros• Modest reduction in

the duration of mechanical ventilation• Increased success of

NIMV• Trend towards shorter

ICU stay

Cons• Hyperglycemia

EVALUATION OF THE STUDY: PROS

• 1st study to confirm the benefits of systemic corticosteroid therapy for ICU patients receiving MV for COPD exacerbation• Validates its usage in clinical practice today•Double-blinded experiment• Source of funding

PROS (CONTINUED)

• Funded by University of Vall d’Hebron Hospital, Laboratory of Experimental Cardiology (LEC)• LEC mission statement: “to contribute to

lessen the impact of cardiovascular diseases on survival capacity and quality of life of the general population by elucidating the mechanisms of disease and proposing new treatments”

EVALUATION OF THE STUDY: CONS

• Results will not have an impact on current clinical treatment practice guidelines• Sample size was small (83)• Length of study (5 years)•Does not mention the effect of the drug on eating behavior

RESOURCE• Alia I, de la Cal MA, Esteban A, et al. Efficacy of corticosteroid therapy in patients with an acute exacerbation of chronic obstructive pulmonary disease receiving ventilatory support. Arch Intern Med. 2011;171(21):1939-1946. Accessed April 13, 2012.

ADDITIONAL THOUGHTS

•What about corticosteroid long-term side-effects?•Optimal dose and length of treatment?•How do the findings translate into practice?

QUESTIONS